title: Maintaining calcineurin inhibition after the diagnosis of post-transplant lymphoproliferative disorder improves renal graft survival.
abstract: Post-transplant lymphoproliferative disorder (PTLD) is an uncontrolled proliferation of transformed lymphocytes fostered by immunosuppression. In addition to chemotherapy, treatment of PTLD includes a reduction of maintenance immunosuppression. Patients with PTLD have an increased risk of graft loss, suggesting that reduced immunosuppression strategy needs to be optimized with regard to graft outcome. Here we retrospectively reviewed 101 cases involving PTLD to identify the risks associated with graft loss. During a median follow-up of 70 months, 39 patients died and 21 lost their graft. Multivariate analysis found that an eGFR under 30 ml/min per 1.73 m(2) at PTLD diagnosis, a biopsy-proven acute rejection episode following reduction of immunosuppression, and the absence of calcineurin inhibition in maintenance immunosuppression are independent risk factors for allograft loss. Neither the type of PTLD nor the chemotherapy regimen was predictive of allograft failure. Histological analysis of graft biopsies showed that maintaining calcineurin inhibition after the diagnosis of PTLD reduced the risk of developing de novo anti-HLA antibodies and humoral rejection. Remarkably, calcineurin inhibitor maintenance was neither associated with higher mortality nor with worse progression-free survival. Thus, maintaining calcineurin inhibition at a reduced dose after the diagnosis of PTLD seems safe and may improve renal graft outcome, possibly through better control of the recipient's humoral immune response.
authors.affiliation: Hospices Civils de Lyon, Hôpital Edouard Herriot, Service de Transplantation, Néphrologie et Immunologie Clinique, Lyon, France.
authors.forename: Jean-Emmanuel
authors.initials: JE
authors.lastname: Serre
authors.affiliation: Service de Transplantation Rénale et de Soins Intensifs, Hôpital Necker, APHP, Paris, France.
authors.forename: David
authors.initials: D
authors.lastname: Michonneau
authors.affiliation: INSERM, U1111, Lyon, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Bachy
authors.affiliation: Laboratoire d'anatomopathologie, Hôpital Necker, APHP, Paris, France.
authors.forename: Laure-Hélène
authors.initials: LH
authors.lastname: Noël
authors.affiliation: 1] Hospices Civils de Lyon, Hôpital Edouard Herriot, Laboratoire d'Immunogénétique, Lyon, France [2] Etablissement Français du Sang, Lyon, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Dubois
authors.affiliation: Laboratoire d'immunologie et d'Histocompatibilité, Hôpital Saint-Louis, APHP, Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Suberbielle
authors.affiliation: 1] Service de Transplantation Rénale et de Soins Intensifs, Hôpital Necker, APHP, Paris, France [2] Université Paris Descartes, Paris, France.
authors.forename: Henri
authors.initials: H
authors.lastname: Kreis
authors.affiliation: 1] Service de Transplantation Rénale et de Soins Intensifs, Hôpital Necker, APHP, Paris, France [2] Université Paris Descartes, Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Legendre
authors.affiliation: 1] Service de Transplantation Rénale et de Soins Intensifs, Hôpital Necker, APHP, Paris, France [2] Université Paris Descartes, Paris, France.
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Mamzer-Bruneel
authors.affiliation: 1] Hospices Civils de Lyon, Hôpital Edouard Herriot, Service de Transplantation, Néphrologie et Immunologie Clinique, Lyon, France [2] INSERM, U1111, Lyon, France [3] Université de Lyon, Lyon, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Morelon
authors.affiliation: 1] Hospices Civils de Lyon, Hôpital Edouard Herriot, Service de Transplantation, Néphrologie et Immunologie Clinique, Lyon, France [2] INSERM, U1111, Lyon, France [3] Université de Lyon, Lyon, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Thaunat
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019703:Calcineurin / Q000502:physiology*; D065095:Calcineurin Inhibitors; D002648:Child; D002675:Child, Preschool; D005260:Female; D005602:France / Q000453:epidemiology; D006084:Graft Rejection / Q000473:pathology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007165:Immunosuppression Therapy; D007223:Infant; D007668:Kidney / Q000473:pathology; D016030:Kidney Transplantation / Q000401:mortality*; D008232:Lymphoproliferative Disorders / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000188:drug therapy* / Q000401:mortality; D012189:Retrospective Studies; D012307:Risk Factors; D055815:Young Adult
chemical_list: D065095:Calcineurin Inhibitors; D019703:Calcineurin